Related Experiment Video
Updated: Apr 4, 2026
Measurement of Lifespan in Drosophila melanogaster
Published on: January 7, 2013
Microbiome contribution to Indy longevity in Drosophila
Danielle N A Lesperance1, Shivani Padhi1, Jacob Macro2
1Department of Molecular and Cell Biology, University of Connecticut, Storrs, CT 06269, USA.
Abstract:
Reduction in the Indy (I'm not dead yet) gene, a plasma membrane citrate transporter, in Drosophila and its homolog in worms extends lifespan by promoting metabolic homeostasis. Indy reduction delays the onset of aging-associated pathology in the fly midgut, including preservation of intestinal barrier integrity and intestinal stem cell homeostasis. Gut microbiota has broad impacts on host metabolism, health, and aging. Age-related dysbiosis impairs intestinal barrier function and drives mortality. However, the underlying mechanisms that link increased microbial load to frailty and negative effects on health remain mostly unclear. Here we show that Indy heterozygote flies have significantly lower bacterial load and increased diversity during aging compared to controls. However, the presence of the microbiome was not required for Indy lifespan extension, though removal of microbes did enhance the effects of Indy reduction on longevity, suggesting potential interactions between the microbiome and Indy. Indy down-regulation was linked to reduced expression of the JAK/STAT signaling ligands Upd3 and Upd2 in the midgut of young flies, which likely contributes to preserved intestinal stem cell homeostasis. Altogether, our results suggest that Indy reduction impacts microbiome load and composition, which preserves gut homeostasis and extends lifespan through impacts on JAK/STAT signaling pathway.
Insights
Reducing the Indy gene in flies extends lifespan by improving gut health and metabolic balance. This intervention lowers bacterial load and enhances microbiome diversity, contributing to longevity.
Area of Science:
- Aging and Longevity Research
- Microbiology and Gut Health
- Molecular Biology and Genetics
Background:
- The Indy (I'm not dead yet) gene, a citrate transporter, is crucial for metabolic homeostasis and its reduction extends lifespan.
- Aging is associated with gut dysbiosis, impaired intestinal barrier function, and increased mortality.
- The mechanisms linking increased microbial load to frailty and negative health outcomes in aging are not fully understood.
Purpose of the Study:
- To investigate the role of Indy gene reduction in modulating gut microbiota composition and its impact on aging and longevity.
- To explore the underlying molecular mechanisms, including JAK/STAT signaling, by which Indy reduction affects intestinal homeostasis.
- To determine the interaction between Indy gene activity and the gut microbiome in promoting healthspan and lifespan.
Main Methods:
- Comparative analysis of gut bacterial load and microbiome diversity in Indy heterozygote flies versus control flies during aging.
- Assessment of intestinal barrier integrity and stem cell homeostasis in Indy-reduced flies.
- Evaluation of JAK/STAT signaling pathway components (Upd3, Upd2) in the midgut of young Indy flies.
- Experiments involving germ-free conditions to assess the necessity of the microbiome for Indy-mediated lifespan extension.
Main Results:
- Indy heterozygote flies exhibited significantly lower bacterial load and increased microbiome diversity during aging compared to controls.
- Microbiome presence was not essential for Indy-mediated lifespan extension; its removal further enhanced longevity.
- Down-regulation of Indy was associated with reduced expression of JAK/STAT signaling ligands (Upd3, Upd2) in the midgut, preserving intestinal stem cell homeostasis.
- Indy reduction delayed age-associated pathology in the fly midgut, maintaining intestinal barrier integrity.
Conclusions:
- Indy gene reduction impacts gut microbiome load and composition, contributing to preserved gut homeostasis and extended lifespan.
- The observed effects are partly mediated through modulation of the JAK/STAT signaling pathway in the gut.
- Interactions between the Indy gene and the gut microbiome play a significant role in regulating aging and longevity.
